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Virology 2007 Mar 1;359(1):105-15

A second-site suppressor significantly improves the defective phenotype imposed by mutation of an aromatic residue in the N-terminal domain of the HIV-1 capsid protein.

Tang S, Ablan S, Dueck M, Ayala-Lopez W, Soto B, Caplan M, Nagashima K, Hewlett IK, Freed EO, Levin JG

Levin JG (reprint author), NICHHD, Mol Genet Lab, Viral Gene Regulat Sect, NIH, Bldg 6B,Room 216, Bethesda, MD 20892 USA NICHHD, Mol Genet Lab, Viral Gene Regulat Sect, NIH, Bethesda, MD 20892 USA US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Bethesda, MD 20892 USA NCI, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, Virus Cell Interact Sect, Frederick, MD 21702 USA NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick Inc, Image Anal Lab, Frederick, MD 21702 USA


The HIV-1 capsid (CA) protein plays an important role in virus assembly and infectivity. Previously, we showed that Ala substitutions in the N-terminal residues Trp23 and Phe40 cause a severely defective phenotype. In searching for mutations at these positions that result in a non-lethal phenotype, we identified one candidate, W23F. Mutant virions contained aberrant cores, but unlike W23A, also displayed some infectivity in a single-round replication assay and delayed replication kinetics in MT-4 cells. Following long-term passage in MT-4 cells, two second-site mutations were isolated. In particular, the W23F/V26I mutation partially restored the wild-type phenotype, including production of particles with conical cores and wild-type replication kinetics in MT-4 cells. A structural model is proposed to explain the suppressor phenotype. These findings describe a novel occurrence, namely suppression of a mutation in a hydrophobic residue that is critical for maintaining the structural integrity of CA and proper core assembly.

Category: Journal Article
PubMed ID: #17055023
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29